Gut Microbiota in the Modulation of Outcomes after Liver Transplant

肠道微生物群对肝移植后结果的调节

基本信息

  • 批准号:
    10231248
  • 负责人:
  • 金额:
    $ 23.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-07 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

Cirrhosis is a major cause of morbidity and mortality, and disease progression is associated with altered gut microbial composition and function. The only reliable cure for cirrhosis is liver transplant (LT). However, a sizable proportion of post-LT patients develop multi-drug resistant organisms (MDROs), cognitive impairment and metabolic syndrome, which can be life- threatening and result in long-term disability or incomplete recovery of pre-LT function. Moreover, using currently available biomarkers, it is unclear which patients will develop these post-LT adverse events and there is some evidence that altered gut microbiota plays an important role. This proposal represents the first step towards using pre-LT microbial modulation in preventing post-LT complications with the central hypothesis: Gut microbial composition and function before liver transplant can successfully predict post-transplant outcomes. We will study this hypothesis using the following specific aims: Aim 1: To determine the role of pre-transplant gut microbial composition and function in the prediction of post-transplant infections through MDRO colonization, Aim 2: To determine the role of pre-transplant gut microbial composition and function in the development of post-transplant metabolic syndrome, Aim 3: To determine the role of pre-transplant gut microbial composition and function in cognitive recovery after liver transplant The study will have 2 parts: Part 1 will utilize already collected longitudinal samples from 150 LT recipients from both centers. Part 2 will enroll 50 more patients per site to validate findings from part 1. Stool microbiota composition (16srRNA sequencing for diversity, relative abundance of potentially pathogenic and beneficial taxa, and specific molecular assays for MDRO colonization) and function (metabolomics, bile acids) will be performed. Cognitive function (validated paper-pencil and computerized techniques) and metabolic syndrome will be diagnosed post-LT. Pre-transplant microbial assessment will be used to predict these outcomes independent of already validated clinical predictors using bio-informatics. This will help guide future precision medicine based research on microbiota in prognosticating LT patients. The CTSAs at VCU and CUIMC are associated with leading LT centers with a long track record of clinical and translational research in cirrhosis, liver transplant, microbiota, and cognition. Both centers will collaborate equally in recruitment and analysis. This proposal fits with PAR-19-100 through the focus on Precision Medicine and Translational studies of the human microbiome.
肝硬化是发病率和死亡率的主要原因,疾病进展与 改变肠道微生物的组成和功能。肝硬化唯一可靠的治疗方法是肝脏 移植(LT)。然而,相当大比例的LT后患者发展为多药耐药, 微生物(MDRO),认知障碍和代谢综合征,这可能是生命- 威胁并导致长期残疾或LT前功能的不完全恢复。 此外,使用目前可用的生物标志物,尚不清楚哪些患者会发生这些 LT后的不良事件,有一些证据表明,改变肠道微生物群发挥作用, 重要的作用这一提议代表了使用LT前微生物调节的第一步 在预防LT后并发症方面的中心假设:肠道微生物组成 和功能可以成功预测移植后的结果。 我们将使用以下具体目标来研究这一假设: 目的1:确定移植前肠道微生物组成和功能在 通过MDRO定殖预测移植后感染, 目的2:确定移植前肠道微生物组成和功能在 移植后代谢综合征的发展, 目的3:确定移植前肠道微生物组成和功能在 肝移植后认知功能恢复 本研究将分为2部分:第1部分将使用已从150 LT中收集的纵向样本 两个中心的接收者。第2部分将为每个研究中心再招募50名患者,以验证 部分1.粪便微生物群组成(16 srRNA测序的多样性,相对丰度, 潜在的致病和有益分类群,以及MDRO的特异性分子测定 定植)和功能(代谢组学、胆汁酸)。认知功能 (经过验证的纸笔和计算机技术)和代谢综合征将在 移植前微生物评估将用于预测这些结果 独立于已经使用生物信息学验证的临床预测因子。这将有助于指导 未来的精准医学基于微生物群的研究,在辅助LT患者中进行。 VCU和CUIMC的CTSA与具有长期跟踪记录的领先LT中心相关 肝硬化、肝移植、微生物群和认知方面的临床和转化研究。两 各中心将在招募和分析方面平等合作。本方案符合PAR-19-100 通过专注于精准医学和人类微生物组的转化研究。

项目成果

期刊论文数量(29)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis.
  • DOI:
    10.1080/19490976.2021.1993584
  • 发表时间:
    2021-01
  • 期刊:
  • 影响因子:
    12.2
  • 作者:
    Bajaj JS;Shamsaddini A;Acharya C;Fagan A;Sikaroodi M;Gavis E;McGeorge S;Khoruts A;Fuchs M;Sterling RK;Lee H;Gillevet PM
  • 通讯作者:
    Gillevet PM
Bristol Stool Scale as a Determinant of Hepatic Encephalopathy Management in Patients With Cirrhosis.
  • DOI:
    10.14309/ajg.0000000000001550
  • 发表时间:
    2022-02-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Duong NK;Shrestha S;Park D;Shahab O;Fagan A;Malpaya Z;Gallagher ML;Morris A;Davis BC;Bajaj JS
  • 通讯作者:
    Bajaj JS
Is it time to spit? More evidence for the oral-gut-liver axis in liver disease.
是时候吐口水了吗?
  • DOI:
    10.1007/s12072-021-10136-3
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    6.6
  • 作者:
    Acharya,Chathur;Bajaj,JasmohanS
  • 通讯作者:
    Bajaj,JasmohanS
Proton Pump Inhibitor Use and Complications of Cirrhosis Are Linked With Distinct Gut Microbial Bacteriophage and Eukaryotic Viral-Like Particle Signatures in Cirrhosis.
质子泵抑制剂的使用和肝硬化并发症与肝硬化中独特的肠道微生物噬菌体和真核病毒样颗粒特征有关。
  • DOI:
    10.14309/ctg.0000000000000659
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    PeñaRodríguez,Marcela;Fagan,Andrew;Sikaroodi,Masoumeh;Gillevet,PatrickM;Bajaj,JasmohanS
  • 通讯作者:
    Bajaj,JasmohanS
Chronic Liver Diseases and the Microbiome-Translating Our Knowledge of Gut Microbiota to Management of Chronic Liver Disease.
  • DOI:
    10.1053/j.gastro.2020.10.056
  • 发表时间:
    2021-01
  • 期刊:
  • 影响因子:
    29.4
  • 作者:
  • 通讯作者:
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Jasmohan S Bajaj其他文献

WED-383 - Serum ammonia levels do not correlate with overt hepatic encephalopathy severity and time to resolution in hospitalized patients with cirrhosis
  • DOI:
    10.1016/s0168-8278(23)00853-x
  • 发表时间:
    2023-06-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jasmohan S Bajaj;Nikolaos T. Pyrsopoulos;Robert Rahimi;Zeev Heimanson;Christopher Allen;Robert Israel;Don Rockey
  • 通讯作者:
    Don Rockey
THU494 - Serum metabolites on admission associate with the development of nosocomial infections in inpatients with cirrhosis
THU494 - 入院时的血清代谢物与肝硬化住院患者医院感染的发生发展相关
  • DOI:
    10.1016/s0168-8278(22)01041-8
  • 发表时间:
    2022-07-01
  • 期刊:
  • 影响因子:
    33.000
  • 作者:
    Jasmohan S Bajaj;Jacqueline O’Leary;Puneeta Tandon;Guadalupe Garcia-Tsao;Patrick S. Kamath;Paul J. Thuluvath;Ram Subramanian;Hugo E. Vargas;Sara McGeorge;Andrew Fagan;Florence Wong;Jennifer Lai;Leroy Thacker;Rajender Reddy
  • 通讯作者:
    Rajender Reddy
THU023 - Active alcohol misuse is linked with lower short-chain fatty acid producing microbiota in a matched study of 450 patients with cirrhosis
THU023 - 在一项针对 450 例肝硬化患者的配对研究中,积极的酒精滥用与短链脂肪酸产生微生物群减少有关
  • DOI:
    10.1016/s0168-8278(22)00643-2
  • 发表时间:
    2022-07-01
  • 期刊:
  • 影响因子:
    33.000
  • 作者:
    Jasmohan S Bajaj;Amirhossein Shamsaddini;Masoumeh Sikaroodi;Brian Davis;Puneet Puri;Michael Fuchs;Andrew Fagan;Sara McGeorge;Patrick Gillevet
  • 通讯作者:
    Patrick Gillevet
FRI-546 - Nosocomial infections in cirrhosis are unpredictable and vary based on region of the world: CLEARED study
  • DOI:
    10.1016/s0168-8278(23)00733-x
  • 发表时间:
    2023-06-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jasmohan S Bajaj;Florence Wong;Qing Xie;Patrick S. Kamath;Mark Topazian;Shiv Kumar Sarin;Shiva Kumar;Sebastián Marciano;Fiona Tudehope;Robert Gibson;Adam Doyle;Stephen Riordan;Alberto Queiroz Farias;Nabiha Faisal;Puneeta Tandon;Marie Jeanne Lohoues;Carlos Benitez;Yongchao Xian;Chuanwu Zhu;Minghua Su
  • 通讯作者:
    Minghua Su
SAT496 - SBP vs. non-SBP bacterial infections at admission have comparable outcomes in a multi-center cohort of inpatients with cirrhosis
在一项多中心肝硬化住院患者队列中,入院时 SAT496 - SBP 与非 SBP 细菌感染的结局相当
  • DOI:
    10.1016/s0168-8278(22)02066-9
  • 发表时间:
    2022-07-01
  • 期刊:
  • 影响因子:
    33.000
  • 作者:
    Jacqueline O’Leary;K.Rajende Reddy;Puneeta Tandon;Patrick S. Kamath;Guadalupe Garcia-Tsao;Flornce Wong;Jennifer C Lai;Ram Subramanian;Paul J. Thuluvath;Benedict Maliakkal;Hugo E. Vargas;Scott Biggins;Leroy Thacker;Jasmohan S Bajaj
  • 通讯作者:
    Jasmohan S Bajaj

Jasmohan S Bajaj的其他文献

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{{ truncateString('Jasmohan S Bajaj', 18)}}的其他基金

Fecal microbiota transplant for Alcohol-Associated Cirrhosis
粪便微生物群移植治疗酒精相关性肝硬化
  • 批准号:
    10703378
  • 财政年份:
    2022
  • 资助金额:
    $ 23.62万
  • 项目类别:
Fecal microbiota transplant for Alcohol-Associated Cirrhosis
粪便微生物群移植治疗酒精相关性肝硬化
  • 批准号:
    10444624
  • 财政年份:
    2022
  • 资助金额:
    $ 23.62万
  • 项目类别:
BCCMA: Targeting Gut Microbiome in Gastrointestinal and Liver Diseases in US Veterans; CMA4: At the Crossroads of the Gut Microbiome, Cirrhosis, and PTSD
BCCMA:针对美国退伍军人胃肠道和肝脏疾病中的肠道微生物组;
  • 批准号:
    10475994
  • 财政年份:
    2022
  • 资助金额:
    $ 23.62万
  • 项目类别:
Liver Cirrhosis Network: Clinical Research Centers
肝硬化网络:临床研究中心
  • 批准号:
    10487561
  • 财政年份:
    2021
  • 资助金额:
    $ 23.62万
  • 项目类别:
Liver Cirrhosis Network: Clinical Research Centers
肝硬化网络:临床研究中心
  • 批准号:
    10700058
  • 财政年份:
    2021
  • 资助金额:
    $ 23.62万
  • 项目类别:
Liver Cirrhosis Network: Clinical Research Centers
肝硬化网络:临床研究中心
  • 批准号:
    10308126
  • 财政年份:
    2021
  • 资助金额:
    $ 23.62万
  • 项目类别:
Gut Microbiota in the Modulation of Outcomes after Liver Transplant
肠道微生物群对肝移植后结果的调节
  • 批准号:
    10054215
  • 财政年份:
    2020
  • 资助金额:
    $ 23.62万
  • 项目类别:
Health IT generated PROs to Improve Outcomes in Cirrhosis
健康 IT 生成 PRO 来改善肝硬化的治疗结果
  • 批准号:
    10374779
  • 财政年份:
    2018
  • 资助金额:
    $ 23.62万
  • 项目类别:
Modulation of Gut-Brain Axis Using Fecal Microbiome Transplant Capsules in Cirrhosis
使用粪便微生物移植胶囊调节肝硬化的肠脑轴
  • 批准号:
    9335590
  • 财政年份:
    2017
  • 资助金额:
    $ 23.62万
  • 项目类别:
Bile Acids and Gut Microbiome in the Pathogenesis of Inflammation in Cirrhosis
胆汁酸和肠道微生物组在肝硬化炎症发病机制中的作用
  • 批准号:
    8994662
  • 财政年份:
    2015
  • 资助金额:
    $ 23.62万
  • 项目类别:

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